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Mice lacking d-amino acid oxidase activity exhibit marked reduction of methamphetamine-induced stereotypy
Atsushi Hashimoto1, Ryuichi Konno, Hiroshi Yano
1Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan. hashimot@is.icc.u-tokai.ac.jp
Abstract:
The behavioral effects induced by methamphetamine (5.0 mg/kg) were compared in the mutant mice lacking d-amino acid oxidase activity and normal mice. The mutant mice exhibited marked decline in the methamphetamine-induced stereotypy compared to the normal mice, whereas the mutant mice displayed a drastic augmentation in the locomotor activity evoked by methamphetamine compared to the normal mice. Because the d-serine levels in the brain of the mutant mice are significantly higher than those in the normal mice, the enhanced d-serine in the brain of the mutant mice could antagonize the methamphetamine-induced stereotypy via the N-methyl-d-aspartate receptors.
Insights
Mutant mice lacking d-amino acid oxidase showed reduced methamphetamine-induced stereotypy but increased locomotor activity. This suggests elevated brain d-serine may counteract methamphetamine
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Methamphetamine induces behavioral changes like stereotypy and locomotor activity.
- D-amino acid oxidase (DAO) metabolizes d-amino acids, including d-serine.
- D-serine acts as a co-agonist at N-methyl-d-aspartate (NMDA) receptors.
Purpose of the Study:
- To investigate the role of d-amino acid oxidase activity in mediating the behavioral effects of methamphetamine.
- To explore the influence of elevated endogenous d-serine on methamphetamine-induced behaviors.
Main Methods:
- Comparison of methamphetamine (5.0 mg/kg) induced behavioral responses in mutant mice lacking DAO activity and normal control mice.
- Assessment of stereotypy and locomotor activity as behavioral endpoints.
Main Results:
- Mutant mice exhibited significantly reduced methamphetamine-induced stereotypy compared to normal mice.
- Mutant mice displayed a marked augmentation in methamphetamine-evoked locomotor activity.
- Brain d-serine levels were significantly higher in mutant mice than in normal mice.
Conclusions:
- The absence of d-amino acid oxidase activity leads to altered behavioral responses to methamphetamine.
- Elevated brain d-serine in mutant mice may antagonize methamphetamine-induced stereotypy through NMDA receptor interactions.
- These findings highlight the modulatory role of d-serine in psychostimulant-induced behaviors.
